Because most human tissues do not regenerate spontaneously, advances in tissue repair and organ regeneration could benefit many patients confronting a variety of medical conditions.
One such advance—a new approach to enhancing normal tissue growth—has been announced by a team of investigators from Beth Israel Deaconess Medical Center and Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. The findings, published in the August 13 issue of the Proceedings of the National Academy of Sciences, could have widespread therapeutic applications.
Although tissue regeneration is a process that is not fully understood, previous research has shown that endothelial cells lining the insides of small blood vessels play a key role in tissue growth. Those same endothelial cells also generate chemical messengers called epoxyeicosatrienoic acids (EETs), which stimulate blood vessel formation in response to tissue injury.
Together with his research colleagues, Dipak Panigrahy, an HMS instructor in pathology, an investigator in Beth Israel Deaconess’s Center for Vascular Biology Research, and the paper’s first author, set out to determine how EETs might participate in organ and tissue regeneration. To do this, they created seven mouse models, each exemplifying a different system: liver, kidney, and lung regeneration; wound healing; corneal vascularization; retinal vascularization; and angiogenesis.
The team used genetic and pharmacologic tools to manipulate EET levels in the animal models, then assessed the role that EETs played in accelerating tissue growth. They found that administering synthetic EETs spurred tissue growth in the research models, while the lowering of EET levels, either by manipulating genes or administering drugs, delayed tissue regeneration.
The team also showed that proteins called soluble epoxide hydrolase (sEH) inhibitors promoted liver and lung regeneration. These proteins are the main metabolizing enzymes of EET and are known to elevate EET levels.
According to Panigrahy, the findings provide a rationale for evaluating sEH inhibitors as novel therapeutics for such conditions as hepatic insufficiency after liver damage, and for diseases characterized by immature lung development, such as bronchopulmonary dysplasia. He also notes that the use of topical sEH inhibitors might help accelerate the healing of skin wounds.